Research Groups
Plant Biology: Insect Resistance
Staff Research Scientist: Nirupama Banerjee, PhD
Group Leader: Raj K. Bhatnagar
Research Interests
Bacterial pathogenesis, Insecticidal toxins, Mycobacterial dormancy, stringent response.
Description of Research
Our broad research interests centre on the interaction of bacterial pathogens with their hosts. In particular, the molecular mechanisms underlying bacterial pathogenecity and virulence factors. We are currently working on an insect pathogenic bacterium Xenorhabdus nematophila and the human pathogen Mycobacterium tuberculosis.
X. nematophila is an insect pathogen that resides as a symbiont in the gut of a soil nematode. Our major focus is the bacterial secretome, which contains a wide spectrum of biologically active molecules. We are specifically interested in identifying novel insecticidal and microbicidal molecules, to study their biology and mode of action in the respective host. The bacterium produces a variety of antibiotics constituting the microbicidal arsenal of this highly prolific soil bacterium. We are investigating a gene pair encoding a bacteriocin protein, released to kill competing bacteria. Presently, we are working out the secretion pathway of the bacteriocin through the flagellar Type III system of X. nematophila.
Mycobacterium tuberculosis has emerged as a successful pathogen infecting millions of worldwide. Our research is focused on understanding the role of toxin-antitoxin (TA) modules in controlling the cell cycle of this intracellular pathogen. A large number of TA loci have been identified in the Mycobacterial genome. Our objective is to study the TA modules that target the replication machinery of the pathogen. The rate of mycobacterial replication varies at different stages of infection in the host. An initial lag phase leads to exponential growth of the bacilli, followed by the stationary phase in which replication is minimal. Pathogenic bacteria are known to survive in this non-replicating state for decades. Thus replication of the pathogen needs precise control for establishing long-term infection and dormancy. The TA genes act as a regulatory system, enabling the bacteria to survive in adverse conditions. We are investigating the TA pairs ParDE, potentially involved in modulation of M. tuberculosis replication. ParE is a DNA gyrase inhibitor and is toxic for the Mycobacterial cell, while ParD acts as antitoxin and controls the parE activity in the cell. In response to an appropriate environmental signal ParD protein is degraded, releasing Par E protein to manifest its toxicity. Thus, by making use of the cell’s own cell-cycle regulatory mechanism, we aim to develop novel drugs against Mycobacteria.
The unique chemistry of the Mycobacterial cell wall is largely responsible for the inherent resistance of the bacterium against various antibiotics, cell-wall active agents and osmotic changes in the environment. It also helps pathogenic mycobacteria to endure stressful conditions encountered in the host. The cell wall of pathogenic mycobacteria is known to contain Poly-L-glutamine, forming an amyloid layer associated with the peptidoglycan. Amyloidogenic proteins have been implicated in the development of several neurodegenarative diseases. Inhibition of polyglutamine synthesis in pathogenic mycobacteria have led to attenuation and increased cell wall sensitivity of the strain. We are currently studying the biological role of polyglutamine in the context of the M. tuberculosis pathogenesis. Our aim is to explore immunomodulatory properties of polyglutamine to understand the infection process for improved antimicrobial therapy.
Recent publications
Chandra, H., Basir, S.F., Gupta, M., Banerjee, N. 2010. Glutamine synthetase encoded by glnA-1 is necessary for cell wall resistance and pathogenicity of Mycobacterium bovis. Microbiology 156, 3669-3677 PubMed link
Kant, S., Kapoor, R., Banerjee, N. 2009. Identification of a catabolite responsive element necessary for regulation of cry4A gene of Bacillus thuringiensis israelensis. J Bacteriol 191, 4687-4692 PubMed link
Chandra, H., Khandelwal, P., Khattri, A., Banerjee, N. 2008. Type 1 fimbriae of insecticidal bacterium Xenorhabdus nematophila is necessary for growth and colonization of its symbiotic host nematode Steinernema carpocapsiae. Environ Microbiol 10, 1285-1295 PubMed link
Joshi, M.C., Sharma, A., Kant, S., Birah, A., Gupta, G.P., Khan, S.R., Bhatnagar, R., Banerjee, N. 2008. An insecticidal GroEL protein with chitin binding activity from Xenorhabdus nematophila. J Biol Chem 283, 28287-28296 PubMed link
Singh, J., Banerjee, N. 2008. Transcriptional analysis and functional characterization of a gene pair encoding iron regulated xenocin and immunity proteins of Xenorhabdus nematophila. J Bacteriol 190, 3877-3885 PubMed link
Banerjee, J., Singh, J., Joshi, M.C., Ghosh, S., Banerjee, N. 2006. The cytotoxic fimbrial structural subunit of Xenorhabdus nematophila is a pore-forming toxin. J Bacteriol 188, 22 PubMed link
